Related Experiment Video

Updated: Jun 1, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Mechanisms of resistance to RAF inhibitors in melanoma

Andrew E Aplin1, Fred M Kaplan, Yongping Shao

  • 1Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. Andrew.Aplin@KimmelCancerCenter.Org

The Journal of Investigative Dermatology
|May 20, 2011
PubMed

Insights

RAF inhibitor therapy shows promise for melanoma but faces resistance. Further research is crucial to understand and overcome acquired and intrinsic resistance mechanisms in BRAF-mutant melanoma patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Personalized cancer therapy has advanced with targeted drugs like RAF inhibitors.
  • PLX4032/RG7204 demonstrated short-term efficacy in late-stage BRAF-mutant melanoma.
  • Tumor re-growth and intrinsic resistance limit long-term success of RAF inhibitors.

Purpose of the Study:

  • To investigate the mechanisms of acquired and intrinsic resistance to RAF inhibitors in melanoma.
  • To identify strategies for overcoming therapeutic resistance in BRAF-mutant melanoma.

Main Methods:

  • Clinical trial data analysis of patients treated with PLX4032/RG7204.
  • Translational research to explore molecular pathways involved in resistance.

Main Results:

  • Initial positive responses to RAF inhibitors were followed by tumor relapse in most patients.
  • A significant subset of patients exhibited intrinsic resistance to the therapy.
  • Mechanisms of acquired and intrinsic resistance remain to be fully elucidated.

Conclusions:

  • RAF inhibitors offer a promising avenue for personalized melanoma treatment but are hampered by resistance.
  • Bi-directional translational research is essential to overcome resistance and improve patient outcomes.

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